دورية أكاديمية
Identification and Characterization of the Amphioxus Lck and Its Associated Tyrosine Phosphorylation-Dependent Inhibitory LRR Receptor.
العنوان: | Identification and Characterization of the Amphioxus Lck and Its Associated Tyrosine Phosphorylation-Dependent Inhibitory LRR Receptor. |
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المؤلفون: | Zhou J; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Xiao Z; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Zhan Y; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Qu X; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Mou S; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Deng C; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Zhang T; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Lan X; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Huang S; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Li Y; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. |
المصدر: | Frontiers in immunology [Front Immunol] 2021 Jun 03; Vol. 12, pp. 656366. Date of Electronic Publication: 2021 Jun 03 (Print Publication: 2021). |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
مواضيع طبية MeSH: | Costimulatory and Inhibitory T-Cell Receptors/*metabolism , Lancelets/*metabolism , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/*metabolism, Animals ; Biomarkers ; Cloning, Molecular ; Costimulatory and Inhibitory T-Cell Receptors/genetics ; Databases, Genetic ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Humans ; Immunophenotyping ; Interleukin-2/biosynthesis ; Jurkat Cells ; Lancelets/genetics ; Lymphocyte Activation ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics ; Phosphorylation ; Rabbits ; Receptors, Antigen, T-Cell/metabolism ; Sequence Analysis, DNA ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism |
مستخلص: | Amphioxus (e.g., Branchiostoma belcheri , Bb) has recently emerged as a new model for studying the origin and evolution of vertebrate immunity. Mammalian lymphocyte-specific tyrosine kinase (Lck) plays crucial roles in T cell activation, differentiation and homeostasis, and is reported to phosphorylate both the ITIM and ITSM of PD-1 to induce the recruitment of phosphatases and thus the inhibitory function of PD-1. Here, we identified and cloned the amphioxus homolog of human Lck. By generating and using an antibody against BbLck, we found that BbLck is expressed in the amphioxus gut and gill. Through overexpression of BbLck in Jurkat T cells, we found that upon TCR stimulation, BbLck was subjected to tyrosine phosphorylation and could partially rescue Lck-dependent tyrosine phosphorylation in Lck-knockdown T cells. Mass spectrometric analysis of BbLck immunoprecipitates from immunostimulants-treated amphioxus, revealed a BbLck-associated membrane-bound receptor LRR (BbLcLRR). By overexpressing BbLcLRR in Jurkat T cells, we demonstrated that BbLcLRR was tyrosine phosphorylated upon TCR stimulation, which was inhibited by Lck knockdown and was rescued by overexpression of BbLck. By mutating single tyrosine to phenylalanine (Y-F), we identified three tyrosine residues (Y539, Y655, and Y690) (3Y) of BbLcLRR as the major Lck phosphorylation sites. Reporter gene assays showed that overexpression of BbLcLRR but not the BbLcLRR-3YF mutant inhibited TCR-induced NF-κB activation. In Lck-knockdown T cells, the decline of TCR-induced IL-2 production was reversed by overexpression of BbLck, and this reversion was inhibited by co-expression of BbLcLRR but not the BbLcLRR-3YF mutant. Sequence analysis showed that the three tyrosine-containing sequences were conserved with the tyrosine-based inhibition motifs (ITIMs) or ITIM-like motifs. And TCR stimulation induced the association of BbLcLRR with tyrosine phosphatases SHIP1 and to a lesser extent with SHP1/2. Moreover, overexpression of wild-type BbLcLRR but not its 3YF mutant inhibited TCR-induced tyrosine phosphorylation of multiple signaling proteins probably via recruiting SHIP1. Thus, we identified a novel immunoreceptor BbLcLRR, which is phosphorylated by Lck and then exerts a phosphorylation-dependent inhibitory role in TCR-mediated T-cell activation, implying a mechanism for the maintenance of self-tolerance and homeostasis of amphioxus immune system and the evolutionary conservatism of Lck-regulated inhibitory receptor pathway. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Zhou, Xiao, Zhan, Qu, Mou, Deng, Zhang, Lan, Huang and Li.) |
References: | Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):5746-7. (PMID: 23553834) J Immunol. 1996 Dec 1;157(11):4751-61. (PMID: 8943376) J Cell Biochem. 1988 Oct;38(2):117-26. (PMID: 3265417) Nat Genet. 2002 May;31(1):100-5. (PMID: 11967531) Sci Signal. 2013 Feb 19;6(263):ra13. (PMID: 23423439) Nature. 1997 Feb 13;385(6617):595-602. (PMID: 9024657) J Exp Med. 1996 Mar 1;183(3):1053-62. (PMID: 8642247) Eur J Immunol. 2013 Dec;43(12):3183-96. (PMID: 24030559) Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):397-402. (PMID: 24368847) Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12338-42. (PMID: 8618896) Front Immunol. 2012 Jun 19;3:167. (PMID: 22723799) Proc Natl Acad Sci U S A. 1995 May 9;92(10):4527-31. (PMID: 7538674) Cell. 2016 Jun 30;166(1):102-14. (PMID: 27293192) Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11810-5. (PMID: 9751747) Proc Natl Acad Sci U S A. 1988 Jul;85(14):5190-4. (PMID: 2455897) Immunity. 1997 Nov;7(5):619-28. (PMID: 9390686) Nat Rev Immunol. 2018 Aug;18(8):485-497. (PMID: 29789755) Science. 2005 Dec 23;310(5756):1970-3. (PMID: 16373579) PLoS One. 2007 Feb 14;2(2):e206. (PMID: 17299586) J Mass Spectrom. 2004 Jan;39(1):38-42. (PMID: 14760611) Front Immunol. 2019 Feb 28;10:314. (PMID: 30873169) Nature. 2003 Mar 13;422(6928):198-207. (PMID: 12634793) Cell. 1992 Aug 21;70(4):585-93. (PMID: 1505025) Immunity. 2007 Sep;27(3):425-37. (PMID: 17719247) Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):15013-8. (PMID: 23980174) Cancer J. 2014 Jul-Aug;20(4):265-71. (PMID: 25098287) Curr Pharm Des. 2009;15(21):2463-70. (PMID: 19601843) J Immunol. 2005 Mar 15;174(6):3493-500. (PMID: 15749885) Science. 2017 Mar 31;355(6332):1428-1433. (PMID: 28280247) Immunity. 2010 Mar 26;32(3):342-54. (PMID: 20346773) Nature. 2004 Jul 8;430(6996):174-80. (PMID: 15241406) Nat Rev Immunol. 2020 Dec;20(12):771-780. (PMID: 32612208) Dev Comp Immunol. 2015 Feb;48(2):297-305. (PMID: 24877655) Front Immunol. 2011 Dec 07;2:72. (PMID: 22566861) Nat Immunol. 2017 Feb;18(2):196-204. (PMID: 27941787) ILAR J. 2005;46(3):241-57. (PMID: 15953832) Annu Rev Immunol. 2002;20:669-707. (PMID: 11861615) Nat Struct Mol Biol. 2014 Feb;21(2):133-42. (PMID: 24463463) J Immunol. 2005 Dec 15;175(12):8138-45. (PMID: 16339552) J Biol Chem. 1996 Mar 29;271(13):7465-72. (PMID: 8631775) PLoS Biol. 2017 Jul 18;15(7):e2002457. (PMID: 28719605) Cell. 1988 Oct 21;55(2):301-8. (PMID: 3262426) |
فهرسة مساهمة: | Keywords: TCR-mediated T cell activation; amphioxus; amphioxus Lck associated LRR (BbLcLRR); immunoreceptor tyrosine-based inhibitory motif; leucine rich repeat receptor (LRR); lymphocyte-specific tyrosine kinase (Lck); tyrosine phosphorylation; tyrosine phosphorylation-dependent inhibitory immunoreceptor |
المشرفين على المادة: | 0 (Biomarkers) 0 (Costimulatory and Inhibitory T-Cell Receptors) 0 (Interleukin-2) 0 (Receptors, Antigen, T-Cell) EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck)) |
تواريخ الأحداث: | Date Created: 20210621 Date Completed: 20210928 Latest Revision: 20210928 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC8211107 |
DOI: | 10.3389/fimmu.2021.656366 |
PMID: | 34149695 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1664-3224 |
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DOI: | 10.3389/fimmu.2021.656366 |